This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. During the reporting period, we have been successful with recruitment demonstrating full feasibility for the project as a whole. We met the initial study goals of 800 detailed interviews with full biological and physiological measures as well as collecting DNA samples and assessment interviews on over 2500 subjects, with several high profile publications. We were then funded for a 5-yr competitive renewal which began 9/1/2010. In the first 4.5 years of this NIMH-supported project, our group collected a large, valuable sample set and demonstrated significant gene-environment interactions in PTSD through our hypothesis-driven efforts in a highly traumatized population. In the competitive renewal, we propose to use state-of-the-art genetic approaches to identify, in a hypothesis-neutral fashion, which genes are the most likely to contribute to PTSD. The proposed genome-wide association study (GWAS) involving N=8,000 subjects will leverage and expand our current set of PTSD samples. Focusing on subjects from a population with similar environmental exposure to a high trauma burden (4000 affected, 4000 unaffected) will allow us to identify a set of genetic variants associated with presence or absence of PTSD symptoms in subjects with a common environmental background. To validate variants associated with PTSD in the proposed GWAS, we will employ additional well-characterized replication samples of traumatized subjects, including 1) a Caucasian sample with N=3,500 traumatized subjects, and 2) a sample of N=2,500 primarily African Americans from St. Louis. We are joining efforts with several other PTSD researchers nationwide for future consortia, to eventually be combined with the N=14,000.